1. Field of the Invention
This invention relates to a novel group of compounds and more particular to a novel group of compounds particularly well suited as sweeteners in edible foodstuff.
2. Description of the Prior Art
Sweetness is one of the primary taste cravings of both animals and humans. Thus, the utilization of sweetening agents in foods in order to satisfy this sensory desire is well established.
Naturally occurring carbohydrate sweeteners such as sucrose, are still the most widely used sweetening agents. While these naturally occurring carbohydrates, i.e., sugars, generally fulfill the requirements of sweet taste, the abundant usage thereof does not occur without deleterious consequence, e.g., high caloric intake and nutritional imbalance. In fact, oftentimes the level of these sweeteners required in foodstuffs is far greater than the level of the sweetener that is desired for economic, dietetic or other functional consideration.
In an attempt to eliminate the disadvantages concomitant with natural sweeteners, considerable research and expense have been devoted to the production of artificial sweeteners, such as for example, saccharin, cyclamate, dihydrochalcone, aspartame, etc. While some of these artificial sweeteners satisfy the requirements of sweet taste without caloric input, and have met with considerable commercial success, they are not, however, without their own inherent disadvantages. For example, many of these artificial sweeteners have the disadvantages of high cost, as well as delay in the perception of the sweet taste, persistent lingering of the sweet taste, and a very objectionable bitter, metallic aftertaste when used in food products.
Since it is believed that many disadvantages of aritificial sweeteners, particularly aftertaste, is a function of the concentration of the sweetener, it has been previously suggested that these effects could be reduced or eliminated by combining artificial sweeteners such as saccharin, with other ingredients such as aspartame or natural sugars, such as sorbitol, dextrose, maltose etc. These combined products, however, have not been entirely satisfactory either. Some U.S. Patents which disclose sweetener mixtures include for example, U.S. Pat. No. 4,228,198; U.S. Pat. No. 4,158,068; U.S. Pat. No. 4,154,862; and U.S. Pat. No. 3,717,477.
Accordingly, much work has continued in an attempt to develop and identify compounds that have a sweet taste and which will satisfy the need for better lower calorie sweeteners. Search continues for sweeteners that have intense sweetness, that is, deliver a sweet taste at low use levels and which will also produce enough sweetness at low levels to act as sole sweetener in all or most sweetener applications. Furthermore, the sweeteners sought must have good temporal and sensory qualities. Sweeteners with good temporal qualities produce a time-intensity sweetness responses similar to natural sweeteners without lingering. Sweeteners with good sensory qualities lack undesirable off tastes and aftertaste. Furthermore, these compounds must be economical and safe to use.
In U.S. Pat. No. 3,798,204 L-aspartyl-O-t-butyl-L-serine methyl ester and L-aspartyl-O-t-amyl-L-serine methyl ester are described as sweet compounds. These compounds, however, are not entirely satisfactory in producing a sweet response at low levels of sweetener.
In U.S. Pat. No. 4,448,716 metal complex salts of dipeptide sweetners are disclosed. In the background of this patent a generic formula is described as an attempt to represent dipeptide sweeteners disclosed in five prior patents: U.S. Pat. No. 3,475,403; U.S. Pat. No. 3,492,131; Republic of South Africa Patent No. 695,083 published July 10, 1969; Republic of South Africa Patent No. 695,910 published Aug. 14, 1969; and German Patent No. 2,054,554. The general formula attempting to represent these patents is as follows: ##STR2##
Wherein R represents the lower alkyls, lower alkyaryls and cycloalkyls, n stands for integers 0 through 5, R.sub.1 represents (a) phenyl group, (b) lower alkyls, (c) cyclo-alkyls, (d) R.sub.2.
Where R.sub.2 is hydroxy, lower alkoxy, lower alkyl, halogen, (e) (S(O).sub.m (lower alkyl) where m is 0, 1 or 2 and provided n is 1 or 2, (f) R.sub.3.
Where R.sub.3 represents an hydroxy or alkoxy and (g) single or double unsaturated cycloalkyls with up to eight carbons. These compounds also are not entirely satisfacory in producing a high quality sweetness or in producing a sweet response at low levels of sweetener.
Dipeptides of aspartyl-cysteine and aspartylmethionine methyl esters are disclosed by Brussel, Peer and Van der Heijden in Chemical Senses and Flavour, 4, 141-152 (1979) and in Z. Lebensm. Untersuch-Forsch., 159, 337-343 (1975). The authors disclose the following dipeptides:
.alpha.-L-Asp-L-Cys(Me)-OMe PA0 .alpha.-L-Asp-L-Cys(Et)-OMe PA0 .alpha.-L-Asp-L-Cys(Pr)-OMe PA0 .alpha.-L-Asp-L-Cys(i-Pr)-OMe PA0 .alpha.-L-Asp-L-Cyst(t-But)-OMe PA0 .alpha.-L-Asp-L-Met-OMe PA0 .alpha.-L-aspartyl-O-(1-methylcyclobutyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-cyclopentyl-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-methylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-ethylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-propylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-isopropylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2-dimethylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,5-trimethylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,2-trimethylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(2,2,5,5-tetramethylcyclopentyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-cyclohexyl-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-methylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-ethylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-propylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-isopropylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2-dimethylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,6-trimethylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,2-trimethylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(2,2,6,6-tetramethylcyclohexyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-cycloheptyl-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-methylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-ethylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-propylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1-isopropylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2-dimethylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,7-trimethylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,2-trimethylcyclohelptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(2,2,7,7-tetramethylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(3-methylcyclohexyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(3-methylcyclopentyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(1-methylcyclopentyl)]-L-threonine methyl ester PA0 .alpha.-L-aspartyl-[O-2,2,5,5-tetramethylcyclopentyl]-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(2,2,6,6-tetramethylcyclohexyl-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,7-trimethylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(1,2,2-trimethylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-O-(2,2,7,7-tetramethylcycloheptyl)-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2,2,5-trimethylcyclopentyl]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2,2-dimethylcyclopentyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2,5-dimethylcyclopentyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2,6-dimethylcyclohexyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-2,2,6-trimethylcyclohexyl]-L-serine methyl ester PA0 .alpha.-L-aspartyl-S-(1-methylcyclobutyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-cyclopentyl-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-methylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-ethylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-propylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-isopropylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2-dimethylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2,5-trimethylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2,2-trimethylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(2,2,5,5-tetramethylcyclopentyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-cyclohexyl-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-methylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-ethylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-propylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-aspartyl-S-(1-isopropylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-isopropylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2-dimethylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2,6-trimethylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2,2-trimethylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(2,2,6,6-tetramethylcyclohexyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-cycloheptyl-L-cysteine methyl ester .alpha.-L-aspartyl-[O-(2,2-dimethylcyclopentyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2,2-dimethylcyclohexyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2,2,4,4-tetramethylcyclobutyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-methylcyclopentyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-methylcyclohexyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-isopropylcyclopentyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-isopropylcyclohexyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-t-butylcyclopentyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-t-butylcyclohexyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(dicyclopropylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(dicyclobutylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(t-butylcyclopropylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(t-butylcyclobutylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(fenchyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(benzyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(.alpha.-methylbenzyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(o-methylbenzyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-furylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(3-furylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-2-(5-methylfuryl)methyl]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(2-thienylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-(3-thienylmethyl)]-L-serine methyl ester PA0 .alpha.-L-aspartyl-[O-2-(5-methylthienyl)methyl]-L-serine methyl ester PA0 .alpha.-L-aspartyl-S-(1-methylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-ethylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-propylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1-isopropylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2-dimethylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2,7-trimethylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(1,2,2-trimethylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-S-(2,2,7,7-tetramethylcycloheptyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(3-methylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(3-methylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2,5,5-tetramethylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2,6,6-tetramethylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(1,2,7-trimethylcycloheptyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(1,2,2-trimethylcycloheptyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2,7,7-tetramethylcycloheptyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2,5-trimethylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2-dimethylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,5-dimethylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,6-dimethylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2,6-trimethylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2-dimethylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2-dimethylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2,2,4,4-tetramethylcyclobutyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2-methylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2-methylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2-isopropylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2-isopropylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2-t-butylcyclopentyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2-t-butylcyclohexyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(dicyclopropylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(dicyclobutylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(t-butylcyclopropylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(t-butylcyclobutylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(fenchyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(benzyl)-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(.alpha.-methylbenzyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(o-methylbenzyl)]-L-cysteine methyl ester PA0 .alpha.-L-asparyl-[S-(2-furylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(3-furylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-2-(5-methylfuryl)methyl]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(2-thienylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-(3-thienylmethyl)]-L-cysteine methyl ester PA0 .alpha.-L-aspartyl-[S-2-(5-methylthienyl)methyl]-L-cysteine methyl ester
European Patent Application No. 34,876 described amides of L-aspartyl-D-amino acid dipeptides of the formula: ##STR3## wherein R.sup.a is methyl, ethyl, n-propyl or isopropyl and R is a branched aliphatic, alicylic or heterocyclic member which is branched at the alpha carbon atom and also branched again at one or both of the beta carbon atoms. These compounds are indicated to be of significant sweetness.
Despite the past efforts in this area, research continues. Accordingly, it is desired to find compounds that provide quality sweetness when added to foodstuffs or pharmaceuticals at low levels and thus eliminate or greatly diminish disadvantages associated with prior art sweeteners.